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. 2025 Sep 19:zwaf586.
doi: 10.1093/eurjpc/zwaf586. Online ahead of print.

Changes in depressive symptoms as predictors of incident cardiovascular disease: insights from four prospective cohorts

Shuang Wu  1   2 , Xu Yang  2   3 , Yang Chen  4   5 , Yimeng Wang  1   2 , Hanyang Liang  1   2 , Wei Xu  1   2 , Juan Wang  1   2 , Xinghui Shao  1   2 , Han Zhang  1   2 , Ziyi Zhong  4   6 , Hongyu Liu  4   7 , Bi Huang  8 , Siqi Lyu  1   2 , Lihui Zheng  2   9
Affiliations

Changes in depressive symptoms as predictors of incident cardiovascular disease: insights from four prospective cohorts

Shuang Wu et al. Eur J Prev Cardiol. .

Abstract

Aims: This study examines how changes in depressive symptoms influence cardiovascular disease (CVD) incidence in diverse aging populations.

Methods and results: Data from four longitudinal cohorts were harmonized: CHARLS (China), ELSA (UK), HRS (US), and MHAS (Mexico). Depressive symptoms were assessed at baseline and follow-up using validated scales, and scores were standardized using z-scores. The primary outcome was incident CVD, defined as a composite of heart attack, angina, congestive heart failure, other physician-diagnosed heart conditions, and stroke. Cox proportional regression analyses assessed the associations between changes in depressive symptoms and CVD risk. Progression from no depression to mild depression was associated with a 28% increase in CVD risk (95% CI: 1.14-1.44), while progression to moderate-to-severe depression was associated with a 23% increase (95% CI: 1.04-1.46). Conversely, remission from mild depression to no depression significantly reduced CVD risk by 19% (95% CI: 0.68-0.98). Improvement from moderate-to-severe depression to mild depression decreased CVD risk by 25% (95% CI: 0.61-0.93), and remission from moderate-to-severe depression to no depression reduced it by 38% (95% CI: 0.50-0.76). Each 1-unit increase in the total depression score raised CVD risk by 12% (95% CI: 1.10-1.14), while each 1-unit increase in depression score change increased risk by 15% (95% CI: 1.11-1.19). Effects were stronger in participants aged <65 years than participants aged ≥65 years.

Conclusion: This multinational cohort study demonstrates that worsening or progression of depressive symptoms increases CVD risk, while remission or improvement confers protective effects, highlighting the need to monitor depression symptom changes in CVD prevention.

Keywords: cardiovascular disease; cohort study; depression; dynamic changes; risk prediction.

Plain language summary

This multinational longitudinal study investigated how changes in depressive symptoms influence the risk of incident CVD across four aging populations from diverse regions (China, UK, US, and Mexico). Utilizing harmonized data from four prospective cohort studies (CHARLS, ELSA, HRS, MHAS; N = 33,437), we found significant associations between depressive symptom changes and CVD incidence. Key findings revealed that: (1) Progression or worsening of depressive symptoms increased CVD risk: progression from no depression to mild depression increased CVD risk by 28% (95% CI: 1.14-1.44), while progression to moderate-to-severe depression raised CVD risk by 23% (95% CI: 1.04-1.46); (2) Improvement or remission of depressive symptoms reduced CVD risk: remission from mild depression to no depression significantly reduced CVD risk by 19% (95% CI: 0.68-0.98); improvement from moderate-to-severe depression to mild depression decreased CVD risk by 25% (95% CI: 0.61-0.93), and remission from moderate-to-severe depression to no depression reduced it by 38% (95% CI: 0.50-0.76). Furthermore, continuous measures demonstrated a robust dose-response relationship, with each 1-unit increase in the total depression score raised CVD risk by 12% (95% CI: 1.10-1.14), while each 1-unit increase in depressive symptom change increased risk by 15% (95% CI: 1.11-1.19). These findings highlight the importance of monitoring depressive symptoms in CVD prevention, and suggest that interventions targeting depressive symptoms may benefit cardiovascular health.

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